Dataset Information

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report.

ABSTRACT: Treatment of chronic graft-versus-host disease is intended to produce a sustainable benefit by reducing symptom burden, controlling objective manifestations of disease activity, preventing damage and impairment, and improving overall survival without causing disproportionate harms related to the treatment itself. Successful management can control the disease until systemic treatment is no longer needed. The complexity of the disease, the extended duration of follow-up needed to observe disease resolution and withdrawal of immunosuppressive treatment, and the lack of fully developed shorter term endpoints impede progress in the field. Identification and characterization of primary endpoints demonstrating clinical benefit without requiring years of follow-up is urgently needed, with the understanding that clinical benefit encompasses not only the self-evident benefit of the primary endpoint but also any other associated benefits. This report discusses regulatory considerations, eligibility criteria, the value of controlled trial designs, the merits of proposed primary endpoints, and key considerations elaborated from experience and progress during the past decade. The report concludes by mapping an overall approach that could support and lead to maximally informative clinical trials, especially those that seek to demonstrate clinical benefit along a pathway to regulatory review and approval.

SUBMITTER: Martin PJ

PROVIDER: S-EPMC4506719 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report.

Martin Paul J PJ Lee Stephanie J SJ Przepiorka Donna D Horowitz Mary M MM Koreth John J Vogelsang Georgia B GB Walker Irwin I Carpenter Paul A PA Griffith Linda M LM Akpek Gorgun G Mohty Mohamad M Wolff Daniel D Pavletic Steven Z SZ Cutler Corey S CS

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20150515 8

Treatment of chronic graft-versus-host disease is intended to produce a sustainable benefit by reducing symptom burden, controlling objective manifestations of disease activity, preventing damage and impairment, and improving overall survival without causing disproportionate harms related to the treatment itself. Successful management can control the disease until systemic treatment is no longer needed. The complexity of the disease, the extended duration of follow-up needed to observe disease r ...[more]

PMID: 25985921

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Project description:Chronic graft-versus-host disease (GVHD) can be associated with significant morbidity, in part because of nonreversible fibrosis, which impacts physical functioning (eye, skin, lung manifestations) and mortality (lung, gastrointestinal manifestations). Progress in preventing severe morbidity and mortality associated with chronic GVHD is limited by a complex and incompletely understood disease biology and a lack of prognostic biomarkers. Likewise, treatment advances for highly morbid manifestations remain hindered by the absence of effective organ-specific approaches targeting "irreversible" fibrotic sequelae and difficulties in conducting clinical trials in a heterogeneous disease with small patient numbers. The purpose of this document is to identify current gaps, to outline a roadmap of research goals for highly morbid forms of chronic GVHD including advanced skin sclerosis, fasciitis, lung, ocular and gastrointestinal involvement, and to propose strategies for effective trial design. The working group made the following recommendations: (1) Phenotype chronic GVHD clinically and biologically in future cohorts, to describe the incidence, prognostic factors, mechanisms of organ damage, and clinical evolution of highly morbid conditions including long-term effects in children; (2) Conduct longitudinal multicenter studies with common definitions and research sample collections; (3) Develop new approaches for early identification and treatment of highly morbid forms of chronic GVHD, especially biologically targeted treatments, with a special focus on fibrotic changes; and (4) Establish primary endpoints for clinical trials addressing each highly morbid manifestation in relationship to the time point of intervention (early versus late). Alternative endpoints, such as lack of progression and improvement in physical functioning or quality of life, may be suitable for clinical trials in patients with highly morbid manifestations. Finally, new approaches for objective response assessment and exploration of novel trial designs for small populations are required.

Dataset Information

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report.

Publications

National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report.

Similar Datasets

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